The purpose of the Mouse Core will be to provide a centralized service oriented facility to insure the capacity of each participating project lab to produce and maintain transgenic and gene-disrupted mice. The Mouse Core will also serve the projects by supporting the infrastructure of a lung injury model that will be extensively utilized by most of the projects, namely exposure to cigarette smoke. As most of the projects propose to make multiple transgenic or gene-targeted lines of mice and to test these lines in the smoking model, the Mouse Core will be an important part of this Program Project Grant. The two primary components of the Mouse Core, the transgenic/knockout production unit and the smoking facility, are both supported by dedicated space within our animal facility and are fully equipped. While not previously part of this Program Project Grant, this core was developed in our Pulmonary Division in 1995 by Dr. Steven D. Shapiro, a project leader on this application, and has been extensively utilized by Project Investigators and Core Directors on this application (Senior, Shapiro, Holtzman, Parks, Shipley). It is staffed by personnel with a collective extensive track record of expertise and productivity in this area. The core has generated over 75 separate transgenic and knockout lines, with multiple founders/chimeras of each. Many of the mice which have been and will be made by this core will facilitate collaborative interactions amongst Project Investigators. As this Program would support 50% of the transgenic/knockout production unit, which will be utilized by Program Investigators as well as other investigators at Washington University, this will allow us to realize an economy of scales and lower production costs per mouse generated.